The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC. The 3.5-angstrom-resolution structure reveals that nine human Integrator subunits and PP2A-AC assemble into a cruciform-shaped central scaffold formed by the backbone and shoulder modules, with the phosphatase and endonuclease modules flanking the opposite sides. As a noncanonical PP2A holoenzyme, the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription. Our study extends the function of PP2A to transcriptional regulation and reveals how dual enzymatic activities—RNA cleavage and RNA polymerase II dephosphorylation—are structurally and functionally integrated into the INTAC complex.

G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines, and G4s are distributed widely across the genome. G4 participates in multiple biological processes including gene transcription, and G4-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, genome-wide studies of the exact roles of G4s in transcriptional regulation are still lacking. Here, we establish a sensitive G4-CUT&Tag method for genome-wide profiling of native G4s with high resolution and specificity. We find that native G4 signals are cell type–specific and are associated with transcriptional regulatory elements carrying active epigenetic modifications. Drug-induced promoter-proximal RNA polymerase II pausing promotes nearby G4 formation. In contrast, G4 stabilization by G4-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. Moreover, ligand-induced G4 stabilization modulates chromatin states and impedes transcription initiation via inhibition of general transcription factors loading to promoters. Together, our study reveals a reciprocal genome-wide regulation between native G4 dynamics and gene transcription, which will deepen our understanding of G4 biology toward therapeutically targeting G4s in human diseases.

An R loop is a unique triple-stranded structure that participates in multiple key biological processes and is relevant to human diseases. Accurate and comprehensive R loop profiling is a prerequisite for R loops studies. However, current R loop mapping methods generate large discrepancies, therefore an independent method is in urgent need. Here, we establish an independent R loop CUT&Tag (Tn5-based cleavage under targets and tagmentation) method by combining CUT&Tag and GST-His6-2×HBD (glutathione S-transferase–hexahistidine–2× hybrid-binding domain), an artificial DNA-RNA hybrid sensor that specifically recognizes the DNA-RNA hybrids. We demonstrate that the R loop CUT&Tag is sensitive, reproducible, and convenient for native R loop mapping with high resolution, and find that the capture strategies, instead of the specificity of sensors, largely contribute to the disparities among different methods. Together, we provide an independent strategy for genomic profiling of native R loops and help resolve discrepancies among multiple R loop mapping methods.

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Traditional power supply method for moving electric railway vehicles is based on contact type power collection technology. This sometimes cannot meet the requirements of modern rail transportation. A new wireless power transfer (WPT) technology can offer significant benefits in modern rail transportation particularly in some stringent environments. This paper reviews the status and the development of rail transit power supply technology, and introduces a new challenging technology-inductive power transfer (IPT) technology for rail transit. Tesla established the underpinning of IPT technology and creatively and significantly demonstrated power transfer by using highly resonant tuned coils long time ago. However, only in recent years the IPT technology has been significantly improved including the transfer air-gap length, transfer efficiency, coupling factor, power transfer capability and so on. This is mainly due to innovative semiconductor switches, higher control frequency, better coil designs and high performance material, new track and vehicle construction techniques. Recent advances in IPT for rail transit and major milestones of the developments are summarized in this paper. Some important technical issues such as coupling coil structures, power supply schemes, segmentation switching techniques for long-distance power supply, and bidirectional IPT systems for braking energy feedback are discussed. Index Terms-Bidirectional energy transfer, inductive power transfer (IPT), magnetic coupling, rail transit, segmented power supply, wireless power transfer (WPT).

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In this paper, a novel pulse density modulation (PDM) with semi-bridgeless active rectifier (S-BAR) in inductive power transfer (IPT) system for rail vehicle is proposed. It is to reduce switching losses of the active rectifier in pickups. In the control method, the insulated-gate bipolar transistors (IGBTs) in the S-BAR are controlled by synchronous PDM signals, so that zero-voltage switching (ZVS) and zero-current switching (ZCS) can be achieved in the whole output power range. The output power is regulated by changing the pulse density (PD) of the S-BAR since the it is almost linear proportional with the PD in high quality factor of pickup side. The communication device between the primary side and pickup side is not necessary anymore. The detailed theoretical analyses of the PDM method are provided, and its advantages are shown in a 7.5kW IPT prototype for rail vehicle. The experimental results are presented to verify the analysis and demonstrate the performance. The overall efficiency of the system by PDM control is 74.2% which is improved by 4% compared with phase shift (PS) control at light load.

Background G-quadruplexes (G4s) are unique noncanonical nucleic acid secondary structures, which have been proposed to physically interact with transcription factors and chromatin remodelers to regulate cell type-specific transcriptome and shape chromatin landscapes. Results Based on the direct interaction between G4 and natural porphyrins, we establish genome-wide approaches to profile where the iron-liganded porphyrin hemin can bind in the chromatin. Hemin promotes genome-wide G4 formation, impairs transcription initiation, and alters chromatin landscapes, including decreased H3K27ac and H3K4me3 modifications at promoters. Interestingly, G4 status is not involved in the canonical hemin-BACH1-NRF2-mediated enhancer activation process, highlighting an unprecedented G4-dependent mechanism for metabolic regulation of transcription. Furthermore, hemin treatment induces specific gene expression profiles in hepatocytes, underscoring the in vivo potential for metabolic control of gene transcription by porphyrins. Conclusions These studies demonstrate that G4 functions as a sensor for natural porphyrin metabolites in cells, revealing a G4-dependent mechanism for metabolic regulation of gene transcription and chromatin landscapes, which will deepen our knowledge of G4 biology and the contribution of cellular metabolites to gene regulation.